Jan is a member of the Cytoskeleton section, and is Assistant Professor in the Department of Biomedical Engineering and the Weill Institute for Cellular and Molecular Biology at Cornell University in New York. He spoke about his lab’s current research on the mutations that can affect the mechanical properties of the cell nucleus and can thereby cause diseases such as muscular dystrophy and may even have a role in cancer metastasis:

Jan’s research particularly focuses on nuclear envelope proteins such as lamins, which have also been associated with cell proliferation. Read Jan’s latest F1000 evaluation of an article that “further forces re-evaluation of the long-held assumption that B-type lamins are essential for cell viability and play an important role in transcriptional repression during differentiation.”

But not everybody is laughing, particularly those on the front lines of donation after cardiocirculatory death (DCD), a practice whereby medical teams remove organs for transplantation from individuals who have recently died.

Of course, this is all well and good – unless the donor is not quite dead.

In a recent article in Philosophy, Ethics, and Humanities, the authors cite many troubling problems with DCD, including unreliable “consensus statements” supporting the practice, unjustifiable premortum procedures that do not benefit the donor, misleading assertions that DCD conforms to current medical procedure and to the law, and conflicts of interest in the DCD process itself. But the most disturbing of the paper’s assertions is that DCD donors may not, in fact, be dead at all.

In his evaluation of the article, F1000 Faculty Member Tom Woodcock writes,

The law’s Dead Donor Rule necessitates some gerrymandering of the definition of death in societies committed to lawful organ donation, and, while other contributors to this debate have called for the rule to be abandoned {1}, Joffe and colleagues take the strict Kantian position that the rule must be observed and veracity demanded of the transplant team, even if this results in fewer donations.

The dead donor rule, write the authors, “claims that humans must be dead before vital organs can be taken, and is intended to prevent the following: patients killed by organ retrieval, harm or exploitation of the weak/vulnerable, mistrust of doctors and transplantation, and treating a patient merely as a means to organs.”

Again, all well and good. However, it’s apparently harder to determine if someone is dead than one might guess.

Let’s consider a person who has given their informed consent to be a DCD donor. It all starts out innocently enough, when, having determined that the time has come, someone pulls the plug on our donor’s life support. If circulation stops within two hours, the individual can be a donor, after which the next two to ten minutes become a frenzy of ambiguity. That’s because death can be declared during this time period, although whether the transplant team uses the two- or the ten-minute rule, or something in between, varies from clinic to clinic. Similarly, the tools and procedures used to confirm death are not standardized between countries or even hospitals.

Then there is the problem of whether the person will stay dead. Irreversibility is one of the prerequisites of declaring death by absent circulation. That said, the authors take pains to distinguish “permanence” from “irreversibility.” Perhaps they capture the dilemma most vividly with this metaphor:

Is a drowning man dead because no one will swim out to save him? Or is he merely going to die?

And let’s not even talk about the Lazarus phenomenon, where previously dead patients come back to life – eerie.

The authors conclude,

…honesty requires that we face these problems instead of avoiding them. Until the concerns we describe are seriously considered, full public disclosure occurs, and fully informed consent is obtained from donors, there should be a moratorium on the practice of DCD.

In other words, don’t bring out your dead. Leave them in there for a while: we may need to rethink our policies.

In lively Socratic repartee, evaluator Tom Woodcock begs to disagree with a strict Kantian approach:

At the altar of the Categorical Imperative and the fully autonomous agent, Kant was also able to justify infanticide, duelling and lethal medical research on convicted criminals. In more modern times, the utilitarian philosopher Peter Singer of Monash and Princeton Universities has argued cogently for medical researchers to use demented humans in preference to sentient great apes {2}. Outlandish conclusions are not incompatible with academic philosophical discourse.

Here, he explains his research focuses, in particular, the cytoskeletal regulation of human macrophages and endothelial cells via actin regulatory mechanisms and intracellular trafficking along microtubules:

Another of their chief lines of research concerns podosomes, actin-rich adhesion structures in macrophages that are a great system with which to study actin turnover because of their many levels of dynamics. Podosomes are adhesion and invasion structures, which makes them relevant to human pathology and physiology.

Read Stefan’s latest F1000 evaluation of a paper that “reveals a new and highly flexible actin-based form of long-range transport and has wide-ranging impact on many aspects of intracellular trafficking.”

Diverging from traditional journal publishing, F1000 Research will offer immediate publication; open, post-publication peer review; open revisioning of work including ongoing updates; and will encourage raw data deposition and publication. In addition, F1000 Research will accept a broad range of article formats and will encourage content types that are now routinely rejected such as negative results, case studies, thought experiments, preliminary analyses, and incomplete datasets.

Our Chairman and founder, Vitek Tracz, said:

The Open Access model has addressed effectively the issue of inadequate access to research findings. It did not address the major issues around communicating the research finding: the delays in access, the inadequacies of peer review, and the complexities of data publishing. It is up to collaboration between researchers and publishers to come up with a solution, and we are determined to be a part of it.

We are still working on many questions as we fine-tune F1000 Research, and so we invite all those working in the bioresearch community, institutions, funders, data centres and repositories, and data mining and informatics groups to join us in open discussion and debate about these outstanding issues – at f1000research.com, via the RSS feed, Twitter: @F1000Research.

Sarah Greene, editor-in-chief of F1000, asked Tom to explain the considerable interest at the meeting about microglia – the resident macrophage-like cells of the brain. He explained how these cells constantly survey the brain for changes in neuronal activity, dysfunction, and cell death:

In the video, Tom also describes his own lab’s research on how microglia react when the nerve fibers of the taste system have been damaged. Finding out more about the complex molecular signaling that goes on between neurons and microglia is important because this may lead to modes of controling inflammatory pain responses and chronic pain.

Tom Finger and fellow Faculty Member Sue Kinnamon co-wrote an F1000 Report last year on how taste receptors can be found not just on the tongue but also in other parts of the body, such as the stomach and airways. A version of their report, with some excellent infographics, was published in the Nov/Dec issue of The Scientist.

Read Tom’s latest evaluation of a research paper he describes as a “roadmap for future studies of interactions between taste and oral trigeminal systems in the brainstem.”

The article, entitled “Toward a new model of scientific publishing: discussion and a proposal” by Dwight Kravitz and Chris Baker of the National Institute of Mental Health at the US NIH, highlights several serious problems with the scientific publishing machine. In particular, the authors note:

• The average 221 days that it takes to get a paper published delays scientific progress as well as young scientists’ careers
• Considering reviewers’ efforts, time spent by authors on revisions, and publication fees, the cost to publish a single peer-reviewed paper in the authors’ field of neuroscience (which publishes some 2,000 papers annually) is over $4,000
• Designed to help publishers prioritize papers, the peer-review system creates an adversarial relationship between reviewers and authors instead of providing useful feedback to authors about the scientific merit of their work.

Most for-profit publishers argue that the review process chaperoned by their editors ensures high standards of scientific research. Not true, argue Kravitz and Baker. “The system is so stochastic and redundant as to be an active hindrance to the progress of research,” they say. Yet the authors are careful not to blame publishers: “This paper is an indictment of the service that we, as a field, ask them to provide.”

How do the authors propose fixing the system? Start by rethinking a publishing model based on limitations that are ancient history. With no need for physical copies of journals, the cost of paper, printing, and distribution has become irrelevant, so publishers could and should guarantee publication for any paper submitted, they say.

Gary Aston-Jones and David Moorman from the Medical University of South Carolina, Faculty Members in the Cognitive Neuroscience section, rate the paper a ‘Must Read‘, and regard the authors’ proposal as “straightforward and results in an improved experience for the entire scientific community.” Aston-Jones and Moorman summarize it this way:

“Reviewers comment and critique on submissions (reviewed in a double-blind fashion) specifically to improve them, publication is typically guaranteed, and a rating system is imposed based on comments of the reviewers and an editorial board with additional interactive reviews continuing after publication to adjust the rated value of the publication. The authors also include additional details such as ways for categorizing published literature to facilitate interaction with existing and future publications with similar subjects. Reviewers are compensated for their efforts and editors compete to attract the best research. The end result is a rapid, unbiased, and complete means of publication of results with built-in filters to assist readers in navigating the growing number of publications.”

The new publishing process that Kravitz and Baker propose “does not completely demolish the existing system, but streamlines it and optimizes it to leverage the currently available technology.” But, they acknowledge, “the process of reforming the current system of publishing will be long, arduous, and fraught with uncertainty.” Indeed.

Editor’s Note: Stay tuned for our announcement next week about F1000 Research, a repository for original research that tackles many of these issues.

In a study published in November in Biological Psychiatry, Morgan used electrode pads to eavesdrop on the heartbeats of 16 two-day-old infants as they spent an hour sleeping alone in a bassinet and an hour sleeping skin-to-skin in their mothers’ embrace. He measured the variation in the gaps between the babies’ heartbeats.

When we are stressed, our autonomic nervous system becomes more active, our hearts beat faster, and the gaps between those beats become more variable. That’s exactly what Morgan saw in the infants who slept alone. They had 176% more variability in their heartbeats than infants who had skin contact with their mothers, suggesting that that they were more easily stressed. They also got just 14% of the quiet sleep that their peers did.

Quiet sleep is important for developing brains. But Morgan doesn’t know if babies would still experience the same dramatic difference in sleep quality after days of sleeping alone, or what the long-term effects of such differences would be. Monkey studies provide a clue: they have repeatedly found that newborns become distressed if they sleep apart from their mother, have higher levels of stress hormones, and behave unusually. They have also shown that these problems persist in the long-term.

Currently, the American Academy of Pediatrics (AAP) advises mothers to sleep in the same room as their babies, but in different beds. For now, it’s too early to say if this advice should be changed. On the one hand, sleeping alone has some clear short-term drawbacks. And throughout our evolutionary history, mothers would have slept in close physical contact with their babies. On the other hand, sleeping together with an infant increases the risk of ‘cot death’, or Sudden Infant Death Syndrome (SIDS) – hence the AAP’s advice.
For now, Morgan himself says that his results should be treated with caution. He wants to repeat a longer version of his experiment, as well as measure the babies’ levels of stress hormones such as cortisol.

“This study is really intriguing because it explores an unknown territory,” says F1000 Faculty Member Donatella Marazziti from the University of Pisa. She notes,

the study underlines the importance of maternal-neonatal skin-to-skin contacts, which is increasingly recommended in neonatal units.

Morgan’s study supports this move.

The article details how 10% to 50% of populations or ecosystems in decline have shown promising recovery trends. This evidence is particularly important because it contradicts the IPSO’s (International Program on the State of the Ocean) high-profile report concluding that the general health of the World’s oceans is in a worse state than previously thought.


Thurston and Pandolfi said,

Our increasing knowledge of this field reveals that humans have had profound impacts upon marine environments for much longer periods of time and often at much greater levels than commonly assumed. Lotze et al. offer a review paper with a refreshingly different focus, that of recovery of populations either as a result of intervention on our part, or because we have reduced levels of habitat destruction and/or exploitation.

The authors identify contributory factors to such recoveries, including reductions in over-fishing, loss of habitat and pollution, an increase in conservation initiatives, management plans and legal protections. The article demonstrates that a full recovery is possible, though former levels of health are rarely ever reached. Still, this happier forecast suggests that, instead of facing oceans full of jellyfish, bleached coral, and nurdles, as some bleaker forecasts have suggested, perhaps our grandchildren will enjoy bountiful fruits of the sea.

(For an informative read about many aspects of human impact on the planet, see ‘The World Without Us’ by Alan Weisman, a book that speculates about the fate of the earth if we were to one day disappear, which explains in part the threat to our oceans from disposable plastics discarded over the last 50 years.)

But what are we to make of those fruit flies hanging around the beer keg? Beer has relatively low sugar content, so what’s their deal? Maybe we should we call a clinic and stage an intervention? Not so fast. According to a new study by Zev Wisotsky, Adrianna Medina, Erica Freeman, and Anupama Dahanukar of the University of California, Riverside, those Drosophila species harboring a copy of the Gr64e gustatory receptor gene are hardwired to hit the sauce. But don’t judge: they’re not chasing the buzz, but rather the glycerol, a sugar alcohol and yeast fermentation byproduct that is also used as an additive in many food products.

F1000 Faculty Member Paul Garrity of Brandeis University writes in his evaluation of the paper:

This very nice study identifies a likely molecular basis for … the predilection of most Drosophila species (like the ever-sensible Drosophila melanogaster) for foods rich in glycerol, which include yeasty concoctions like beer, and it probes why not all Drosophila species share this affinity. The difference appears to reside in the Gr64e gustatory receptor locus.

The authors found that flies with the Gr64e gene exhibited both cellular and behavioral reactions to glycerol. On the behavioral side, the investigators found that proboscis extension was “robust” in reaction to glycerol as opposed to sugar, as long as the Gr643 receptor locus was functional, and that the flies preferred glycerol to sugar across a range of glycerol concentrations.

On the cellular side, the researchers were also able to express Gr64e in non-gustatory, olfactory neurons. When they did so, the altered neurons reacted to glycerol, where they had not before. The authors also tested whether fruit flies without a sense of smell (ΔOrco mutant flies) would still be attracted to beer. They were, pointing to the fact that flies’ preference for Bass Pale Ale is a gustatory, not an olfactory phenomenon.

To quote my favorite heading from the paper’s Results section, “Beer drives a strong ingestion response.”

This paper points to an interesting potential evolutionary shift in appetite preferences in fruit flies. So does that mean that the next time you’re presented with a choice between a candy bar and a glass of zinfandel, and you choose the zinfandel, you can chalk it up to your DNA? Until we know for sure, at least we can take heart in having something in common with fruit flies besides a mutual affection for bananas.

Figshare uses creative commons licensing (CC0 for the datasets; CC-BY for everything else) so others can re-use the data whilst allowing authors to maintain their ownership. Like F1000 Posters, the value for science is in the discoverability of scientific content that has been otherwise largely hidden. The movement towards efficient, open, collaborative science has been relatively slow, as with all cultural changes, and requires both ‘carrots and sticks’. UK Science Minister David Willets recently stated:

“Our starting point is a commitment by the coalition to transparency and open access to publicly funded data”

and there are now sustained and increasing efforts from governments worldwide to encourage researchers to share their research data. As Mark Hahnel, creator of figshare points out:

“figshare has focused on providing immediate ‘carrots’ for researchers, demonstrating how they can improve their career prospects through open science. By taking advantage of traditional measures of impact (i.e. the number of citations), as well as new measurements such as altmetrics, researchers get a greater level of information about the impact and reach of their research. By getting some real-time measurements of the impact of their research, they don’t necessarily have to wait for other researchers to cite it using traditional methods.”

Researchers can further increase the reach of their outputs via various social media platforms through ‘share buttons’ throughout the site. There is much talk about how social media has the potential to benefit research through real-time discussion of the science you did today, not last year when you first submitted your paper. Although it is well known that the uptake of online commenting on papers on publisher’s sites has been rather slow, it appears that researchers may be more inclined to use social media platforms and blog and tweet about novel research away from the publisher’s site, as shown by the volume of such links within the upcoming altmetric.com tool, as well as recent research done by Jason Priem and colleagues.

The idea of breaking research publications into their smallest unit is also appealing as it enables search engines, such as Google, to index the title of each individual research object, making the work more discoverable. Browse and filter options, and lists of most-shared and most-viewed work in each research field are then intended to give some idea of which work, within that field, may be having the biggest impact in real-time.

Figshare provides each researcher with 1GB of free private storage space, and the option to purchase further space is apparently coming soon. This space can be used to manage your research data, and then make it available to the public when you choose with a click of a button. Until then, your research objects are backed up in the cloud, and accessible from anywhere. Researchers are encouraged to add descriptions, tags (e.g. grant numbers) and links to their uploads, be it private or public, to ease navigation through large amounts of research data.

As an increasing number of groups and organisations push to encourage researchers to release and share their data, it will be interesting to see how well this tool, together with other new approaches (including our own upcoming plans; more very shortly…), can help to change the existing culture and working practices in a way that can only be a positive for research as a whole.

Contrary to what the poorly pigmented among us might expect, the link shown here is not related to greater intensity of UV rays at midday, but to our own circadian clock’s control over DNA damage repair.

That a link exists between the circadian circuitry and onset of other adverse health events, such as asthma and heart attacks, is well known. And studies of mouse liver and brain tissue by other UNC researchers have shown in recent years that the core molecular circadian clock controls the protein XPA (xeroderma pigmentosum group A), which is involved in DNA damage repair (PNAS, Feb 24, 2009; PNAS, March 16, 2010).

In “Control of skin cancer by the circadian rhythm,” (PNAS, Nov 15, 2011), Shobhan Gaddameedhi and colleagues explain that “UV radiation produces two major lesions in DNA … thought to be the primary cause of skin cancer in humans.” A process known as nucleotide excision repair removes the lesions, and the aforementioned circadian-controlled XPA is one of six crucial factors in that process.

Through experiments on hairless mice, the authors showed that the same UV dose is more carcinogenic in hours of the day when the animal’s circadian rhythm slows down nucleotide excision repair. For nocturnal mice, DNA repair activity is at its slowest in the wee hours of the morning, when DNA replication, conversely, is at its most aggressive. Exposure to UVR between 4am and 6am led to a higher frequency of cancer development among the research animals. The authors say the findings imply that, for diurnal humans, afternoon sun exposure is likely more highly carcinogenic.

According to F1000 evaluator Bruce Demple, who rates the paper a “must-read”:

The most striking result in the paper shows that UV-induced skin cancer occurs about 5-fold more frequently when the UV exposure occurs during the time of minimum nucleotide excision repair activity compared to exposure when nucleotide excision repair is maximal.

To be sure, the consequences of total dysfunction of the excision repair genes are known to be severe: skin cancer occurs 5,000 times more frequently on the sun-exposed skin of those who inherit mutations, resulting in the syndrome Xeroderma pigmentosum. But, the authors acknowledge that DNA damage and repair are just two of many factors that impact cancer development and, they note, “cancer is a multistage process and a long-term endpoint of a specific incident.” For the structural biology and cancer research communities, they recommend further studies with repair-deficient and clock mutant animals to “deconvolute the relative contributions of the various pathways to the rhythmicity of the carcinogenic effect of UVR.”

Their recommendation for the rest of us? If you must sunbathe, get it out of the way early in the morning, when your body’s repair capacity is at its best.

A new study published in the latest issue of Fertility and Sterility warns that the Wi-Fi from your laptop could make you infertile.

The article was selected by Martine Nijs, Faculty Member in Diabetes & Endocrinology, who emphasised that this is the first study to demonstrate a clear negative influence of laptop Wi-Fi on both sperm motility and sperm DNA integrity. She warned,

Men should be cautious about using a laptop for extended periods of time not only because these computers generate heat and can increase scrotal temperature {1} that is deleterious to spermatogenesis but also because, as shown here, the active Wi-Fi connections could induce DNA damage in their spermatozoa.

Ouch.

Of course, it’s not only men whose fertility is negatively affected by modern lifestyles. A study from November last year reports that a lack of vitamin D might impact negatively upon the female reproductive system. Bryan Larsen, Faculty Member in Women’s Health, highlighted this article, saying,

The complexity of vitamin D’s actions results in part from the fact that it modulates the activity of thousands of genes, so may influence many aspects of pregnancy and parturition that may or may not involve calcium metabolism.

So just another two more things to add to the growing list of modern issues that could affect fertility. Already on the list are cigarettes, mobile phones, obesity and – bizarrely – botox.

Creativity is
A) Good.
B) Bad.

Did you choose option A? Of course you did, because nobody would say they hate creativity – it would be like saying you hate the special olympics. But a new study, “The bias against creativity: why people desire but reject creative ideas”, by Jennifer S. Mueller (The Wharton School), Shimul Melwani (University of Pennsylvania), and Jack A. Goncalo (Cornell University) reveals a hitherto unknown ambivalence about creativity that lives under the surface, camouflaged, like a suckerfish. According to their paper, people experiencing uncertainty tend to hold an unacknowledged negative bias against creativity. Furthermore, those holding such a bias also have more difficulty recognizing a creative idea when they encounter one.

In this study, the authors conducted two experiments, in which each had a designated “uncertainty” group (members in this group were told they could receive extra money, but that it would be distributed via lottery. Stressful.). Experiment 1 tested the subjects’ reaction to words representing creativity vs. practicality. Experiment 2 had the participants write essays on creative problem-solving, and then rate the creativity and practicality of a new running shoe.

Both experiments uncovered a hidden negative bias against creativity in the uncertainty group. Furthermore, the uncertainty group rated the novel shoe idea as less creative than did the control group.

While reading this study, I was reminded of the fact that both the US TV channels HBO and Showtime passed on the show “Mad Men” before it went on to become a hit series on AMC. Certainly, many such examples exist in the arts world. And, of course, there are plentiful such stories from science: think heliocentrism and continental drift. In biology, think Margulis’ theory of endosymbiosis and McClintock’s jumping genes.

Faculty of 1000 member Eduard Stange writes in his evaluation of the article that such biases are not confined to the distant past:

Quite recently, it took years for the Helicobacter theory of ulcer disease to be accepted, and I was one of the skeptics. Similarly, even this year’s Harrison’s Principles of Internal Medicine discusses Crohn’s disease in terms of dysregulated adaptive immune response and ignores the overwhelming evidence for a defective barrier.

And the uncertainty effect may not be limited to individual decision-making. As the authors write:

If people hold an implicit bias against creativity, then we cannot assume that organizations, institutions, or even scientific endeavors will desire and recognize creative ideas even when they explicitly state that they want them.

Oh boy. So what are the creatively inclined to do? It seems that the problem is not a supply of creative ideas, but rather how to gain acceptance for those ideas already out there in circulation. Therefore, the authors conclude that,

…the field of creativity may need to shift its current focus from identifying how to generate more creative ideas to identifying how to help innovative institutions recognize and accept creativity.

In other words, we need more scientific AMCs to pick up the slack that the HBOs leave behind.

Tobet’s lab differs slightly from other labs in that they look at this area from the perspective of the developing blood-brain barrier. In general, the development of the blood-brain barrier is influenced by neurotransmitters, and their research specifically focuses on how the neurotransmitter gamma-amino butyric acid (GABA) affects blood vessel ingrowth into this area of the brain.

This is important because a defect in the developing blood-brain barrier may allow molecules to enter the brain that would normally be shut out, and these molecules may become contributing factors to the development of disease pathologies.

Tobet predicts that there will be a lot more research focus on neurovascular development in the future.
Related Sections:Neuroscience, Neurological disorders, Videos, Faculty Members

These signatures purportedly hint at how healthy cells transform into tumours in the first place. If, for example, the genes in question are involved in wound healing, this tells you that the healing process is somehow involved in a tumour’s progression. These collections of genes reveal deeper truths about the disease they’re associated with.

This idea sounds reasonable, but David Venet from the Université Libre de Bruxelles has thrown a big spanner into the works. He has shown that completely random sets of genes can predict the odds of surviving breast cancer better than published signatures.

Venet found three signatures that are completely unconnected to cancer. Instead, these collections of genes were associated with laughing at jokes after lunch, with the experience of social defeat in mice, and with the positioning of skin cells. All of them were associated with breast cancer outcomes.

It got worse. Venet collected 47 breast cancer signatures from published papers and compared them to sets of random genes. The random sets were equally (or more) strongly associated with breast cancer outcomes than 60% of the published ones. In fact, you can randomly select a group of 100 genes or more, and be 90% sure of finding a statistically significant link with breast cancer. Venet wrote, “Investigators are bound to find an association however whimsical their marker is.”

Venet’s study was described as a “must-read” by F1000 member Jinfeng Liu from Genentech Inc. The results may seem unbelievable, but there is a simple reason for them. The activities of thousands of genes across a breast cancer cell’s genome are related to how quickly that cell proliferates (grows and divides). And that is related to a patient’s prognosis.

As an analogy, you could find hundreds of things that correlate with a person’s wellbeing and lifespan: the number of Apple products they own, whether they have university degrees, how many cars they have, and so on. But this doesn’t mean that these things improve our health; instead, they reflect how wealthy we are, our lifestyle choices, and our access to good healthcare.

Gene signatures may be relatively useless at illuminating the causes of cancer, but the team stresses that they can still help doctors – after all, they’re still related to prognosis. Writing in The Scientist, the study’s lead author Vince Detours says, “Smoke does not drive fire, yet it is powerful indicator of when and where a fire is burning.”

Detours also aims a blow at scientific publishers who have let studies of genetic signatures proliferate uncontrollably. He wrote:

It took us four years and six rejections to get this work finally published in a computational biology journal – not the most efficient venue to reach the oncology community. Meanwhile, a steady stream of studies confounded by proliferation rates has appeared.

He added,

This has to be said; one can no longer stay silent about the rather limited self-correction capability of the top tier publishing system (Cell, Nature Genetics, PNAS, etc.), which promoted these studies in the first place.

Dr Epstein, a public health expert and physician at Harvard Medical School, is perhaps best noted for his work linking infectious diseases and climate change. He worked with the Intergovernmental Panel on Climate Change (IPCC), the National Academy of Sciences (NAS), the National Oceanic and Atmospheric Administration (NOAA) and the National Aeronautics and Space Administration (NASA) to assess the health impacts of climate change. Epstein also devoted much time to speaking publicly on the subject and stirred much political debate.

In an obituary appearing in the New York Times, Al Gore praised him as a researcher and for “his rare ability to communicate the subtleties and complexities of his field.” As further reported in the NY Times, he devoted much of his career as a doctor working in poor communities and as a volunteer in east African countries. He considered it a responsibility to educate the public that climate change is “not just about whales, wolves, and polar bears,” according to his friend and compatriot, Dr Eric Chivian of the Center for Health and the Global Environment at Harvard.

Read Paul Epstein’s F1000 evaluations here.

Not on any of these lists, but the focus of a study by Roth et al. from the Montefiore hospital in New York, are pediatric oncologists. The authors investigated levels of ‘career burnout’ – a work-related syndrome involving emotional exhaustion, depersonalization, and diminished feelings of personal accomplishment; frighteningly, 72% in this job group say they experience at least moderate levels of burnout and 38% experience high levels. As Maciej Murawski and Piotr Czauderna point out in their evaluation, this doesn’t account for those who might be suffering from the condition but are unaware of it. Burnout was also found to be more prominent in women than men (47% vs. 32%), especially among those who have been working under 10 years (50% vs. 33%). The hours in clinical care, work-life balance and, most of all, the emotional rigors of the job equate to an incredible investment of time and energy.

The buildup of a certain amount of personal scar tissue is almost unavoidable in a medical career, but this article throws open an important question: are we doing enough to support doctors? According to Roth et al.’s results, only 40% of institutions have a service in place to help with burnout, clearly inadequate as greater demands are placed on health services around the world by expanding populations and shrinking budgets.

We spoke with a pediatric oncologist who serves as an F1000 Faculty Member, who observed, “the idea that experiencing burnout is a weakness, not to be openly discussed, persists in pediatric oncology.” Yet as the Roth article shows, forums for debriefing and services to help with burnout are associated with lower rates of the condition, so getting the community to open up to the problem could yield a significant benefit.

Our source believes there is one key area for improvement that could help tackle this issue head on:

Trainees in pediatric oncology receive little training in strategies to deal with the stress of caring for children with cancer and their families… Improved trainee education about this issue may be an effective strategy both to reduce the chance that pediatric oncologists in training experience it and to break down the misconception that it is a weakness not to be openly acknowledged.

Though on a more positive note: “Strong connections and meaningful relationships with children and their families can be very rewarding, which can in turn be protective against burnout. So, some of the very things that may increase the risk for burnout are also the things which can protect against it.”

We’d like to hear from you about burnout in your discipline and what support you’ve experienced (if any), so do let us know. And finally, in case you were wondering, the least stressful job is …………. medical records technician. Apparently these professionals don’t have the time or inclination to read the stories of patients between the lines.

Leishmaniasis under a microscope

The research, led by Sanger Institute scientists working with colleagues in India, Nepal, Belgium, London, Glasgow, and Berlin, describes the use of next-generation sequencing technologies to produce a high-quality reference sequence of one line of L. donovani. Comparisons among 16 more clinical lines isolated from patients in Nepal uncovered clues about the evolution of drug resistance in the strain.

The work, published in December in Genome Research, is notable for its success using rapid new sequencing technologies to bring genomic knowledge to epidemiological studies in the field. The authors note that efforts to eliminate visceral leishmaniasis in Bangladesh, India, and Nepal have been hampered by L. donovani’s drug resistance. Epidemiological studies point a re-emergence of the disease in the region since DDT-spraying campaigns in the 1960s. Though the varieties of L. donovani are relatively homogenous, their susceptibility to antimonial drugs is highly variable. The authors’ whole genome sequence data revealed genetic structure that was not shown by multilocus typing within the 17 strains and suggested that drug resistance has emerged multiple times in the closely related set.

Their study also documented, for the first time, extensive variation in chromosomal copy number on a genome-wide basis in clinical lines. Parsons, whose own lab at the Seattle Biomedical Research Institute studies cell structure and function of parasites including leishmaniasis, writes:

While the field has suspected that chromosomal copy number was somewhat variable in Leishmania, this study shows it is perhaps more rampant than thought, with only 9 of the 36 chromosomes appearing to be disomic in all strains. The copy number plasticity clearly has relevance for the evolution of drug resistance now and for future drugs.

The authors conclude that dynamic selective pressures resulting from changes in drug policy on the Indian subcontinent are likely to “mould the genome of this parasite.” Their approach proves the usefulness of new sequencing technologies for creating a reference and then monitoring the evolution of any parasite from within an affected region.

His lab has been studying the B cell antigen receptor (BCR) since the 1970s and was involved in the initial characterization of the BCR signaling pathways. This led to an interest in the regulation of BCR signaling, in particular the mechanisms behind anergy in B cells, e.g. in type 1 diabetics.

In addition, Cambier’s lab is interested in the effects of aging on B cells and how virus infection of an organism leads to a long period of immune unresponsiveness in B cells.

His latest evaluation for F1000 highlights a related paper suggesting that carriers of the PTPN22 risk allele have intrinsic defects in B cell tolerance, which predisposes them to the development of autoimmune disease.

Read more of Cambier’s evaluations.

The randomized controlled study on 120 adults without dementia, published in PNAS last year, investigated whether a one-year aerobic exercise programme could improve hippocampal volume. Participants were randomly assigned to an exercise or a stretching control group. After one year, the exercise group showed an increase in left and right hippocampal volume by 2.12% and 1.97% respectively, while the stretching control group presented a decrease of 1.40% and 1.43%. Gomez remarked,

[This study] provides some of the first direct experimental evidence in humans that aerobic exercise both improves memory function and increases anterior hippocampal volume.

Interestingly, this article not only shows how exercise could be used to improve memory but also how fitness is protective against age-related memory loss. This could mean that exercise can be used as a low-cost intervention to prevent dementia in the elderly and even improve memory from year to year.

In a related video from SFN, Wendy Suzuki, a Faculty Member in our Cognitive Neuroscience section, tells us about her research in humans into whether aerobic exercise can improve learning and memory.

She said,

This is a new area of research trying to identify the pattern and the kinds of exercise that are most beneficial [for memory and cognitive function] … [using] EEG and fMRI studies to try and understand exactly what brain areas may be affected.

“I am saddened that you have decided to leave the F1000 team of Faculty Members, and I take seriously your criticisms of the limited value you feel the service provides to its users in identifying significant papers. I do not quite agree with them, and I am happy when the occasion comes to discuss these with you, but I can assure you we do work hard to make the service better, more systematic, more comprehensive and improve it in many other ways.

What I want to address here is what seems to be your main reason for resigning, namely that you think F1000 is committing some mortal sin by charging subscription and not being free to all. The Open Access model of publishing was developed by us and others to ensure that research findings are available free and without restriction to all. It was made possible by changing the model of charging the reader to one charging the author, or rather in both cases the relevant institutions and funders. This model cannot apply sensibly to providing information that is not primary research findings. The relevant institutions would not accept a scheme like that and in my opinion rightly so. If we want to provide a range of “secondary” services in an organised way, services that actually require significant investment to make them happen, we must fall on the option of charging the reader. If someone will find a way to do it without charging anyone (such as the examples you plan to support from now on rather than F1000) and do it better, we will just lick our wounds and go away quietly. Until that time, a very large team here and the many thousands of Faculty of 1000 members will continue to do what we can to do the best possible evaluation system we can invent.”

Many of us have been involved in introducing and developing Open Access to publishing research results in biology and medicine. I, and many of my colleagues in F1000, have been involved in launching BioMed Central, as well as collaborating with others in making OA the reality it is today. This was done against the wishes of many interested parties, including established publishers, learned societies, and many researchers who saw it as potentially undermining existing systems of publishing. We have invested and risked more than anyone in trying to find a sustainable commercial model for OA, without which we felt it would be in danger of failing.

OA is not free. In the somewhat closed system of the research community, where all involved both write and read research papers, all the services are paid for primarily by the funders and institutions. The importance of changing the traditional scheme of “readers pay” to “authors pay” was not to destroy commercial publishing, but to find a way to ensure that access to research findings is universally free. OA is not necessarily significantly cheaper than traditional publishing, and it is paid for by the same funders and institutions that pay for traditional publishing. The reason that OA succeeded (after quite a long time and significant changes to the methodology) is primarily because the funders of research decided it is in their interest to insure broadest distribution of the research findings they paid for.

I do not believe it is possible or reasonable to convince funders and institutions to pay for all publishing and other services to the research community and offer them to all users freely, and the idea that there is something immoral in offering services by subscription is wrong. Developing a service like F1000 is very expensive (we are working on it for a long time and we are yet to break even), and if we do find that the need for it is not sufficient we will simply not survive. If other services will grow which can provide the same or similar services free to all, we will be unnecessary and will have to admit defeat. This is always the risk of developing a new service as it was when we started BioMed Central. At this point we do feel convinced that we are offering a service of quality and value, that we can respond to the changing needs and grow a service worth having.

We do plan to start publishing primary research findings in the near future (we are now going through intensive discussion with many researchers about how best to do this, and have started a related repository of posters), and all this will be fully Open Access and financed the same way OA publications are financed today. We believe that it is essential for primary research findings to be free to all, and we also believe that there is a place for publishing groups to develop paid for secondary services (books, reviews, teaching, etc.). The research community needs both.

[F1000 editor-in-chief Sarah Greene writes: Now, and until Jan 3, we invite readers to peruse the entire library of over 115,000 evaluations without charge, to judge the caliber of recommendations written by our 10,000+ Faculty Members and their Associates. Meanwhile, we wish our Members and subscribers a happy new year and many thanks for their continuing support and thought-provoking comments.]

Pertwee is the 19th recipient of this award, presented every two years by the British Pharmacological Society. He is one of the world’s leading cannabinoid scientists, having discovered potential new therapeutic uses for compounds called phytocannabinoids that are produced by cannabis. Pertwee said,

Just some potential new uses we have recently discovered are for the treatment of certain liver disorders, Parkinson’s disease, stroke and drug dependence.

Editorial director of F1000 Biology, Kathleen Wets, met up with him last week at the British Pharmacological Society (winter) meeting. Here he talks to Kathleen about his award-winning research on cannabinoids:

We’re focusing particularly on a compound called cannabidiol and on another compound called tetrahydrocannabivarin, or THCV, which has interesting properties because it can target the same receptors that are targeted by our endogenous cannabinoids but in a slightly different way. It blocks one set of these receptors but activates the other set, and that could be very important for treating disorders like liver diseases and so on.

Pertwee recently evaluated an article for F1000 which also investigated cannabinoid receptors in the brain of mice. The article strongly supports the involvement of these receptors in cocaine’s effects on brain function and identified a likely role for these receptors in the pharmacotherapy of drug abuse and addiction. Read the evaluation here.

See more of Roger Pertwee’s evaluations.

Finger and Kinnamon discuss their findings in a F1000 Biology Report, as well as in an article published in the latest edition of The Scientist magazine. They speculate on the different roles that these taste receptors could play:

Despite the similarities in receptor molecules and signaling cascades, … these seemingly misplaced taste-like pathways do not, however, give rise to sensations of taste, though they appear to detect compounds known to elicit a taste response in the mouth.

So, the taste transduction cascade is not restricted to the sensation of taste per se or even to systems regulating food intake. In fact, it’s widely thought that the receptors mediating taste transduction are a chemodetection system in a variety of organ systems. In the gut for example, sweet sensations could trigger the release of insulin, while bitter sensations in the colon could elicit the secretion of anions, leading to fluid secretion into the intestine, in turn resulting in diarrhea.

In the video below, Sue Kinnamon talks to editorial director Kathleen Wets at the Society for Neuroscience 2011, about her and Tom’s research:

Our editor-in-chief, Sarah Greene, also caught up with Tom Finger at SFN, and below he tells us about the research relevant to his work that has caught his interest.

Read Finger and Kinnamon’s F1000 Biology Report.

At that time, Owen had shown through fMRI studies that some coma patients, who were previously presumed to be unconscious by virtue of being physically unresponsive to any stimulus, actually had awareness. Images captured through fMRI showed blood flow indicating normal brain activity in response to specific questions and commands. Owen suggested that as many as 20% of “vegetative state” patients might be misdiagnosed.

Despite the astounding implications for thousands of such patients worldwide, many will never undergo fMRI screening. Beyond the expense and limited availability of scanners that make it a prohibitive procedure, many patients who have suffered traumatic injuries have metal plates or pins that disqualify them as MRI candidates. Or, lacking bodily control, they are unable to remain still long enough for useful images to be captured.

In a recent article “Bedside detection of awareness in vegetative state: a cohort study” published in The Lancet (Nov 2011), Owen and Cruse now employ a low-cost, portable technology – electroencephalography (EEG; which has been around for 100 years) – to detect consciousness at the patient bedside. Instead of blood flow, EEG measures electrical current in the brain of a patient. Each of their subjects, with EEG nodes attached to their scalps, were asked 200 times in 20 minutes to imagine squeezing their hand into a fist and to imagine wiggling their toes.

The study of 16 vegetative state patients confirmed Owen’s previous estimate that some 20 percent of people whose behavior would indicate otherwise do actually have awareness – they can hear, understand, and respond to commands. In one televised news interview Cruse said that, though EEG is not a new technology, “the advance is making use of machine learning to interpret the patterns of brain activity.” The studies present the possibility that, for the cost of an electric wheelchair, families could use an EEG at home to “actually have a conversation with a patient who externally doesn’t have ability to communicate,” he said.

F1000 reviewer Nicolas Bruder calls the work exceptional, but warns that, though the authors claim that EEG is cheap, can be done at the bedside, and is available almost everywhere, there is a learning curve that might preclude use by families at home:

The methods used to generate the appropriate stimulus and interpretation of the data need training, time, and neurophysiological and neurocognitive expertise to avoid biases or misinterpretation of the data.

Bruder also points out one curious aspect of the study: While 3 of 16 “vegetative” patients were able to generate appropriate EEG responses to stimulus, three controls – volunteers from the university’s School of Social Sciences – for some reason, did not. This shows that “a negative EEG finding should be interpreted with caution.”

Nevertheless, these discoveries are significant enough to indicate that a change in the clinical classification of disorders of consciousness may be needed. Bruder writes:

There may be some patients with a state of severe ‘functional locked-in syndrome’ after brain injury who will need specific medical management compared to vegetative state or minimally conscious state patients.